IllnessNail dysplasia, congenital; differential diagnosis

NGS +

Congenital and hereditary nail disorders are a heterogeneous group of rare diseases. They may occur as non-syndromic congenital nail disorders or in various genetic syndromes, e.g., nail-patella syndrome, pachyonychia congenita, ectodermal dysplasia, epidermolysis bullosa, T-cell immunodeficiencies. Congenital nail disorders should not be confused with the physiologic, transient nail changes seen in most newborns, which usually resolve in the first few months of life. Congenital isolated anonychia is rare and is caused by RSPO4 variants. Iatrogenic congenital anonychia +/- digital hypoplasia may be due to prenatal phenytoin exposure. Non-syndromic congenital nail disease 1 (FZD6) presents with thickened, hyperplastic, and hyperpigmented nails with a very slow growth rate that develop as claw-like structures. In hereditary leukonychia (porcelain nails, PLCD1), leukonychia punctata or striata presents. Isolated congenital nail clumping is rare and characterized by enlargement of the nail plate and distal segments of the fingers and toes (HPGD, SLCO2A1; each associated with primary hypertrophic osteoarthropathy). Many other nonsyndromic congenital nail disorders have been described with mostly unknown genetic alterations. Tennis racket nails/thumbs can be an isolated disorder or syndromic with numerous genetic disorders. Several multiple malformation syndromes are associated with nail hypoplasia, anonychia/micronychia. Autosomal inheritance patterns are generally observed. A negative molecular genetic test result does not exclude the clinical suspicion for an inherited nail disease.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1280/

https://www.ncbi.nlm.nih.gov/books/NBK1304/

https://www.ncbi.nlm.nih.gov/books/NBK1132/

https://www.ncbi.nlm.nih.gov/books/NBK1112/

• Anonychia congenita (RSPO4)
• CHAND [Curly hair-ankyloblepharon-nail dysplasia] syndrome (RIPK4)
• Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, AD (EDAR)
• Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, AR (EDAR)
• Ectodermal dysplasia 3, Witkop type (MSX1)
• Ectodermal dysplasia 4, hair/nail type (KRT85)
• Ectodermal dysplasia 7, hair/nail type (KRT74)
• Ectodermal dysplasia 9, hair/nail type (HOXC13)
• Ectodermal dysplasia/short stature syndrome (GRHL2)
• Nail disorder, nonsyndromic congenital, 1 (FZD6)
• Nail disorder, nonsyndromic congenital, 3 [leukonychia] (PLCD1)
• Nail-patella syndrome (LMX1B)
• T-cell immunodeficiency, congenital alopecia, nail dystrophy (FOXN1)
• T-cell lymphopenia, infantile, with/-out nail dystrophy, AD (FOXN1)
• Toenail dystrophy, isolated (COL7A1)